Recent investigations have indicated that the use of phenobarbital either alone or in conjunction with chenodeoxycholic acid may be beneficial in effecting changes in gallbladder bile and making it less lithogenic. Normal volunteers had biliary lipid parameters and bile lipid composition determined both before and after the administration of phenobarbital. Biliary lipid parameters (hepatic cholesterol secretion, hepatic phospholipid secretion, bile acid secretion, gallbladder bile lipid composition, and the composition of individual bile acid species in gallbladder bile) showed no changes between the period of phenobarbital ingestion compared to the period when phenobarbital was not being ingested. It was concluded that phenobarbital did not significantly alter any parameters of the biliary lipid metabolism and does not appear to be a useful agent when used alone for the prevention or dissolution of cholesterol gallstones in man.